But that’s not what the studies found. To expose the confusion about what these studies show, let’s start with what they did and what they reported.

South Africa study: The first study to report was carried out in South Africa during 2002-05. The study team solicited men willing to be circumcised, then on a random basis assigned half the men to an intervention group to be circumcised first and the other half to a control group to remain intact (uncircumcised) until the end of the study. The study team then followed and retested the men – circumcised and intact – at scheduled visits over as long as 2 years.

During follow-up, 20 men in the intervention (circumcision) group got HIV at the rate of 0.85% per year, while 49 men in the control (intact) group got HIV at the rate of 2.11% per year. If all the men’s infections came from sex, this is good evidence that circumcision cuts men’s risk to get HIV from sexual partners from 2.11% to 0.85% per year.

But did all or even most infections come from sex? Not according to evidence the study collected and reported. Twenty-three of the 69 men with new infections said they had no sexual partner or always used condoms from their last HIV-negative test to their first HIV-positive test. Men reporting no sexual risks got HIV at the rate of 1.11% per year. If these men are telling the truth, they apparently got HIV from blood during injections, dental care, tattooing, and other skin-piercing events. If men with no sexual risks got HIV from blood, it’s likely that men with sexual risks also got at least some of their HIV infections from blood contact. The rate of getting new HIV infections in men who reported at least one unprotected (without a condom) sex event was 1.86% per year, only 0.75% faster than for men reporting no sexual risks. The modestly faster rate to get HIV in men with vs without sexual risks explains less than 1/3 of the men’s infections (using standard epidemiologic analyses and terms, the crude population attributable fraction of incident HIV associated with having any vs no unprotected sex is 27%).

The study team could have done a better job identifying the sources of men’s infections if they had asked more questions and reported more data. But where is the failure? Did they not ask, or are they not telling? Like most studies on HIV risk in Africa, this study has not provided public access to collected raw data (with safeguards to protect participants’ confidentiality). Also, like most studies on HIV risk in Africa, this study has not disclosed its questionnaire and data collection forms – so there is no public record of what information they collected and chose not to report (chose to withhold).

From the published record, it’s likely that some crucial evidence about sexual risks was simply not collected – for example, there is no indication the study team traced and tested any of the men’s sexual partners. There were not a lot of partners to trace: 4 men with spouses got HIV, and 55 men who reported 0-1 non-spousal partners got HIV.

Notably, both reported measures of possible exposure to HIV through skin-piercing procedures had a bigger impact on a man’s risk to get HIV than did possible exposure to HIV during sex (having any vs no unprotected sex). The study’s reported measures of blood-borne risks are vague: The study team has not said what procedures men got at clinics treating genital health problems. The team has also not reported HIV incidence separately for injections, for transfusions, and for hospitalizations. The study has not reported other skin-piercing health care procedures, such as infusions or dental care, and we don’t even know if they collected such information. The study has also not reported any data on skin-piercing cosmetic procedures; did they ask?

Table 1: What information on sex and blood risks did the three studies collect and report for men with and without new HIV infections?

Risks for HIV

South Africa, 2002-05

Kenya, 2002-06

Uganda, 2003-06

Blood-borne risks

Injections

Collected but not reported

Unknown

Unknown

Transfusion

Collected but not reported

Unknown

Unknown

Hospitalization

Collected but not reported

Unknown

Unknown

Injections, transfusions and/or hospitalization

RR=1.7

Unknown

Unknown

Visiting a clinic for a genital health problem

RR=6.8

Unknown

Unknown

Infusions

Unknown

Unknown

Unknown

Dental care

Unknown

Unknown

Unknown

Scarification

Unknown

Unknown

Unknown

Other blood risks

Unknown

Unknown

Unknown

Sexual risks

Any vs. no partners

Collected but not reported

Collected but not reported

RR=2.4

<100% condom use

Collected but not reported

Collected but not reported

RR=1.1

Any vs no partners or <100% condom use

RR=1.7

Collected but not reported

RR=1.6

Any vs no non-spouse partner

Collected but not reported

Collected but not reported

Collected but not reported

HIV status of spouse

Not collected

Not collected

Collected but not reported

HIV status of non-spouse partners

Not collected

Not collected

Not collected

Sources: see references in the text. RR: crude hazard ratio (calculated as the rate of getting HIV with the risk divided by the rate without the risk).

Kenya study: The Kenya study, 2002-06, was similar in design to the South Africa study. The study circumcised some men, then followed and retested circumcised and intact men for as long as two years to see who got HIV. Nineteen men in the intervention (circumcised) group got HIV at the rate of 1.9% over two years, while 46 men in the control (intact) group got HIV at the rate of 4.1% over two years.

How many of the 65 men got HIV from sex? The study reports information on sexual behavior vs HIV for only 7 men infected during the first three months of follow-up. Five of these seven men reported no sexual partners from the time they entered the trial (using sensitive tests, the study could not find HIV in blood collected then) until their first HIV-positive test after 1-3 months. Four of the men with early infections had been circumcised in the study clinic. All four were found with HIV one month after their circumcision; three reported no sexual partners in that month. Contaminated local anesthetic or contaminated instruments could have infected the men during circumcision – the study team could have investigated the possibility, but there is no indication they did so.

What about the other 58 infections? The study asked men about sexual partners and condom use throughout the trial, but does not report this information for men with and without new HIV infections. The study team has said nothing about tracing and testing men’s sexual partners – did they do it and not report it, or just not do it?

But how did the men get HIV? Six men with new HIV infections reported having no sex partners during the period between their last negative and first HIV-positive test. Ten others with new infections reported always using condoms. Taken together, the 16 men who reported no possible sexual exposure to HIV got HIV at the rate of 0.72% per year – presumably from skin-piercing events that exposed them to HIV in blood. Men who reported any unprotected sex acquired HIV at the rate of 1.17% per year, only 0.45% per year faster than men reporting no sexual risks. As in South Africa, the marginally faster rate at which men who reported sexual risks got HIV explains less than a third of the infections observed during the trial (using standard epidemiologic analyses and terms, the crude population attributable fraction of incident HIV associated with having any vs no unprotected sex is 29%).

Based on the study team’s partial disclosure of collected information on sexual risks, most infections came from skin-piercing events. To determine the sources of the men’s infection, it is relevant to know about skin-piercing events in men who did and did not get HIV. However, as in the Kenya study, the Uganda study team provides no report of what data were collected on skin-piercing procedures, and discloses no collected data on skin-piercing procedures.

Ethical short-comings: The three studies treated research participants in ways that would not be allowed in the US and France, the countries that funded the studies.

The South Africa study recruited men and the Uganda study recruited wives without insisting they hear their HIV test results. Neither study has said how many people the study followed who did not hear their results. This would not be allowed in the US, where a condition of recruitment in studies that follow people to see who gets HIV is that participants must be willing to hear their test results.

The design of the Uganda study allowed the study team to follow wives who did not know they were HIV-positive to watch them infect men who did not know they were at risk. The study allowed this to happen because it tested and recruited wives without insisting they hear their test results, and without insisting they share those results with their husbands. This would also not be allowed in the US – where regulations ask that doctors and counselors warn spouses if the HIV-positive partner will not do so. The study has not said how many unsuspecting men got HIV from wives the study knew were infected.

None of the studies insisted that men who acquired HIV bring their wives for couple counseling. This ethical lapse – leaving wives with unknown risks – undermined the objective of the research, which was to see how much circumcision reduced sexual transmission. Bringing in and testing wives after men got HIV would not only protect HIV-negative wives, but would also provide information about how many infections came through sex, and how much circumcision reduced HIV from sex.

Table 2: Ethical short-comings in the three trials

Ethical issue

South Africa, 2002-05

Kenya, 2002-06

Uganda, 2003-06

Did the study enroll people who refused to hear their HIV status?

Yes

No

No

Did the study follow men not aware their wives had tested HIV-positive?

No

No

Yes

Did the study insist that men who got HIV during the trial bring their wives for couple counseling?

No

No

No

Mass circumcision based on assumption, not evidence: Campaigns for mass circumcision in Africa began in 2007, shortly after three studies – in Kenya, South Africa, and Uganda – concluded that circumcision cut men’s risk to get HIV by 51% to 60% by reducing men’s risk to get HIV from sexual partners.

Those conclusions are based on assumption, not evidence. According to what men reported about sexual behavior in two trials, only a minority of their infections came from sex. It is, of course, possible that men lied about their sexual behavior. But with that argument, realize what has happened: The $1.5 billion enterprise to circumcise 20 million men in Africa is no longer based on evidence. It’s based on assuming away evidence. It’s based on a prior belief – inconsistent with evidence from these trials – that almost all HIV infections in African adults come from sex.

15 responses to “Denied, withheld, and uncollected evidence and unethical research cloud what really happened during three key trials of circumcision to protect men”

This is scandalous! Ethical comparison with Tuskegee or the Guatemala syphilis
experiments is appropriate. The scandal continues with mass circumcision of men and
boys with ill-informed consent (often by coercion or even force) using this seriously flawed data as an excuse.

There are several things from these trials that do not make much sense. Coming into the South African trial with the number of men who were found to be HIV-infected at enrollment, the average age of these men and the average age of the onset of sexual activity the baseline risk of HIV infection was 1.02 per 100 person-years. So it is not clear why, over the next two years, the risk doubled to 2.1 per 100 person-years in the control group. Using this historical control, the risk was only slightly reduced in the intervention group by 0.17 per 100 person-years (1.02 minus 0.85). Over two years, the number needed to treat would be 294 to “prevent” one infection.

So what happened in the control group that their HIV-risk suddenly doubled? No one seems to be answering this question.

In the Ugandan study, men who consistently used condoms had higher infection rates than those who reported never using condoms. In the control group the rate of infection was 1.08 per 100 person-years for those who never used condoms and 1.49 per 100 person-years in those who consistently used condoms. So, would the take-home lesson from this study be to recommend that condoms never be used?

The Uganda study was less forthcoming in providing data on the risk of infection in those who were not having sex or always using condoms. The only data provided are for the six men who should not have become infected, which accounts for an infection rate of 0.48 per 100 person-years.

In the Kenyan study, given the number of men who were found to be HIV-infected at enrollment, the average age of these men and the average age of the onset of sexual activity the baseline risk of HIV infection was 1.94 per 100 person-years. During the trial, the risk of infection was 1.00 per 100 person-years in the intervention group and 2.12 per 100 person-years in the control group.

The Kenyan study also was less forthcoming in providing data on the risk of infection in those who were not having sex or always using condoms. There were 5 men who should not have become infected and account for a rate of 0.73 per 100 person-years.

Interesting that with the little data that they disclosed that the validity of the their studies crumbles. It would be interesting to see what full disclosure of their data would reveal. Two of these studies were paid for with my tax dollars through the NIH, so the data should be available to the public.

In about 2001 Robert Bailey, the main author of the Kenya study, predicted in advance that his study would show efficacy, according to one article. “Dr. Bailey and his colleagues now intend to conduct a randomized, controlled trial of circumcision in Kenya. The study will compare HIV acquisition rates in 1000 control subjects who will remain uncircumcised with those of 1000 subjects who will be circumcised as part of the study. Bailey’s group estimates that a study of this size will demonstrate the benefits of the approach within 2 years.” Myron S Cohen, MD, “Circumcision as an HIV Prevention Intervention,” http://medscape.com/viewarticle/418368, accessed 4/8/2010 and 02/17/12. Perhaps these studies were “self-fulfilling prophecies.” Are the researchers intentionally concealing the real facts? The public certainly has a right to full disclosure.

Circumcision for boys is obviously not medically necessary. If it were, it would be common in most countries throughout the world, whereas it is actually in the minority. If boys needed to be circumcised, it would be common in the UK, France, Italy, Spain, Greece, Sweden, Norway, Denmark and many other countries. The question is, why are Americans so attracted to circumcision compared to the rest of the Western countries? Why does circumcising boys have such a strong cultural hold in America? I’ve been surprised at how many non-Jewish Americans I’ve met who consider circumcising their boys essential.

I think it’s a combination of reasons, Troy. First is the US’s unique fascistic medical/state relationship. There’s a lot of profit to be made in circumcising non-consenting children. Second is the US’s political ties to the Middle East – Zionism has a strong grip in the upper echelons of US foreign policy and government, and one way to symbolize control over a tribe is to have them mark their children in this way. Third reason is the most powerful of all – American men are in denial that their sexual organs have been needlessly mutilated. So they must invent new reasons for it as often as possible, and downplay their loss in sexual enjoyment and function.

The three trials found a marked reduction in HIV incidence among the men who were circumcised against the men who weren’t.

If your hypothesis is that some of the infections were not sexually acquired, then the protective effect of circumcision for men in heterosexually acquired HIV is actually GREATER than what was observed – not less – unless you want to propose some mechanism by which circumcision might protect against HIV acquired through unsterile dental care, tattooing, injections, etc.

Hi Patricia,
Thanks for your comment.
The point I tried to make above is that there is too much reliance on speculation, due in large part to study teams denying, avoiding, and withholding relevant evidence. African men and policy-makers need evidence to make good decisions.
But If you wish, let’s play with hypotheses.
If your hypothesis is true — that circumcising men reduces their risk to get HIV through their penis by more than 50%-60% — then why did the study teams not do a better job finding and reporting relevant evidence? They clearly want to promote circumcision — so why didn’t they trace and test sexual partners? If someone has evidence behind them, don’t you usually expect them to lay it all out? Why are they not doing so?
But let’s suppose — for the sake of argument — that your hypothesis is true. Where does that get us? Consider: National surveys in 5 African countries (Cameroon, Ghana, Malawi, Rwanda, and Zimbabwe) find that circ’ed men are more likely to be HIV-positive vs intact men (see: https://dontgetstuck.wordpress.com/circumciseion-intact-living-with-hiv/). So if your hypothesis is true — that circ’ing cuts men’s risk to get HIV through the penis by more than 50%-60% — then most HIV-positive men in those countries got HIV some other way. It also means that circ’ing men could be expected to have little impact on their overall risk to get HIV as well as on HIV epidemics.
You ask me to speculate about how intact men might be more likely than circ’ed men to get HIV from blood exposures. I prefer facts, but OK, here’s some speculation: The study teams might be telling men that circing protects them from sexually transmitted infections. Intact men might be scared that every (imaginary) itch is a sexual infection and go for injections. Clinic staff with the same idea might be giving intact men more injections.
But why are we still speculating when data are or could be available? Instead of asking me to speculate, why not ask study teams to report all their data? Decades ago we could have moved beyond speculation to explain Africa’s HIV epidemics — If researchers had done their jobs. Simply done their jobs. Nothing stupendous or insightful. Just trace infections to find where they’re coming from.

What if non-circumcised men are more likely to seek medical treatment – whether for foreskin-related ailments, or some other reason (such as less fear of doctors?) – and hence get infected through medical equipment?

The Journal of Law and Medicine, has published a new critique of those three randomized clinical trials from Africa that have purported to find that male circumcision reduces female-to-male sexual transmission of HIV by 60 percent.

This critique finds numerous flaws in the execution of these studies and finds that the absolute reduction in HIV transmission is about 1.3 percent, not the claimed 60 percent. The 1.3 percent is not considered to be clinically significant.

This is offset by a 61 percent relative increase in male-to-female HIV transmission when the male partner is circumcised.

Given this, the three RCTs should not be used in the formulation of public health policy.

Thanks Gregory. I don’t see the attached PDF, could you supply it as a link or send it to me and I’ll put it on the site so it can be accessed by anyone who wishes to read it. Also, what was the absolute increase in male to female transmission as a result of male circumcision?